Ida Biunno

@article{baronchelli_epigenetic_2017,

title = {Epigenetic and transcriptional modulation of WDR5, a chromatin remodeling protein, in Huntington's disease human induced pluripotent stem cell (hiPSC) model},

author = {Simona Baronchelli and Alberto {La Spada} and Aikaterini Ntai and Andrea Barbieri and Paola Conforti and Gloria Saccani Jotti and Serena Redaelli and Angela Bentivegna and Pasquale {De Blasio} and Ida Biunno},

doi = {10.1016/j.mcn.2017.04.013},

issn = {1095-9327},

year  = {2017},

date = {2017-05-01},

journal = {Molecular and Cellular Neurosciences},

volume = {82},

pages = {46--57},

abstract = {DNA methylation (DNAm) changes are of increasing relevance to neurodegenerative disorders, including Huntington's disease (HD). We performed genome-wide screening of possible DNAm changes occurring during striatal differentiation in human induced pluripotent stem cells derived from a HD patient (HD-hiPSCs) as cellular model. We identified 240 differentially methylated regions (DMRs) at promoters in fully differentiated HD-hiPSCs. Subsequently, we focused on the methylation differences in a subcluster of genes related to Jumonji Domain Containing 3 (JMJD3), a demethylase that epigenetically regulates neuronal differentiation and activates neuronal progenitor associated genes, which are indispensable for neuronal fate acquisition. Noticeably among these genes, WD repeat-containing protein 5 (WDR5) promoter was found hypermethylated in HD-hiPSCs, resulting in a significant down-modulation in its expression and of the encoded protein. A similar WDR5 expression decrease was seen in a small series of HD-hiPSC lines characterized by different CAG length. The decrease in WDR5 expression was particularly evident in HD-hiPSCs compared to hESCs and control-hiPSCs from healthy subjects. WDR5 is a core component of the MLL/SET1 chromatin remodeling complexes essential for H3K4me3, previously reported to play an important role in stem cells self-renewal and differentiation. These results suggest the existence of epigenetic mechanisms in HD and the identification of genes, which are able to modulate HD phenotype, is important both for biomarker discovery and therapeutic interventions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{la_spada_cell_2016,

title = {Cell Line Macroarray: An Alternative High-Throughput Platform to Analyze hiPSC Lines},

author = {Alberto {La Spada} and Simona Baronchelli and Linda Ottoboni and Francesca Ruffini and Gianvito Martino and Nunzia Convertino and Aikaterini Ntai and Tobias Steiner and Ida Biunno and Andrea {De Blasio}},

doi = {10.1369/0022155416673969},

issn = {1551-5044},

year  = {2016},

date = {2016-12-01},

journal = {The Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society},

volume = {64},

number = {12},

pages = {739--751},

abstract = {In the past decade, tissue microarray (TMA) technology has evolved as an innovative tool for high-throughput proteomics analysis and mainly for biomarker validation. Similarly, enormous amount of data can be obtained from the cell line macroarray (CLMA) technology, which developed from the TMA using formalin-fixed, paraffin-embedded cell pellets. Here, we applied CLMA technology in stem cell research and in particular to identify bona fide neogenerated human induced pluripotent stem cell (hiPSC) clones suitable for down the line differentiation. All hiPSC protocols generate tens of clones, which need to be tested to determine genetically stable cell lines suitable for differentiation. Screening methods generally rely on fluorescence-activated cell sorting isolation and coverslip cell growth followed by immunofluorescence; these techniques could be cumbersome. Here, we show the application of CLMA to identify neogenerated pluripotent cell colonies and neuronal differentiated cell products. We also propose the use of the automated image analyzer, TissueQuest, as a reliable tool to quickly select the best clones, based upon the level of expression of multiple pluripotent biomarkers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{baronchelli_investigating_2015,

title = {Investigating DNA methylation dynamics and safety of human embryonic stem cell differentiation toward striatal neurons},

author = {Simona Baronchelli and Alberto {La Spada} and Paola Conforti and Serena Redaelli and Leda Dalpr{à} and Pasquale {De Blasio} and Elena Cattaneo and Ida Biunno},

doi = {10.1089/scd.2015.0057},

issn = {1557-8534},

year  = {2015},

date = {2015-10-01},

journal = {Stem Cells and Development},

volume = {24},

number = {20},

pages = {2366--2377},

abstract = {The potential use of human embryonic stem cells (hESCs) in cell-based therapies points out the critical importance of epigenomic evaluation for cell-based therapies. Specifically, DNA methylation appears to be a crucial player in establishing cell fate commitment and lineage choices. In this study, we report the global changes observed on the CpG islands distributed in promoters, gene bodies, and intergenic regions and the major biochemical pathways and genes involved in methylation changes as H9-hESCs turn into a neuronal culture containing medium-sized spiny striatal neurons (MSNs). Using an ontogeny-recapitulating protocol of striatal neuron differentiation, we analyzed DNA methylation profiles during the conversion from pluripotency to neuropotency up to the acquisition of a mature neuronal phenotype. H9-hESCs changed the methylation pattern both through de novo methylation and hypomethylation of specific gene promoters. Bioinformatic analysis allowed us to identify a panel of striatal-associated genes, which were regulated by DNA methylation and differentially expressed during striatal commitment. Importantly, DNA methylation analysis revealed that H9-hESCs did not acquire methylation-based oncogenic properties after differentiation. Indeed, hypermethylation of cancer-associated genes that characterize transformed cells, such as Polycomb repressive complex-associated genes, was not detected in the neuronal cultures. However, the oncosuppressor gene, BCL2L11, became hypermethylated in H9-hESC-derived mature neurons. Whole-genome DNA methylation profiling could become a technological platform to predict the differentiative potential of hESC-derived cultures and establish further biosafety assessment quality control tools of the cell-based products.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{mellai_sel1l_2015,

title = {SEL1L SNP rs12435998, a predictor of glioblastoma survival and response to radio-chemotherapy},

author = {Marta Mellai and Monica Cattaneo and Alessandra Maria Storaci and Laura Annovazzi and Paola Cassoni and Antonio Melcarne and Pasquale {De Blasio} and Davide Schiffer and Ida Biunno},

doi = {10.18632/oncotarget.3611},

issn = {1949-2553},

year  = {2015},

date = {2015-05-01},

journal = {Oncotarget},

volume = {6},

number = {14},

pages = {12452--12467},

abstract = {The suppressor of Lin-12-like (C. elegans) (SEL1L) is involved in the endoplasmic reticulum (ER)-associated degradation pathway, malignant transformation and stem cells. In 412 formalin-fixed and paraffin-embedded brain tumors and 39 Glioblastoma multiforme (GBM) cell lines, we determined the frequency of five SEL1L single nucleotide genetic variants with regulatory and coding functions by a SNaPShot™ assay. We tested their possible association with brain tumor risk, prognosis and therapy. We studied the in vitro cytotoxicity of valproic acid (VPA), temozolomide (TMZ), doxorubicin (DOX) and paclitaxel (PTX), alone or in combination, on 11 GBM cell lines, with respect to the SNP rs12435998 genotype. The SNP rs12435998 was prevalent in anaplastic and malignant gliomas, and in meningiomas of all histologic grades, but unrelated to brain tumor risks. In GBM patients, the SNP rs12435998 was associated with prolonged overall survival (OS) and better response to TMZ-based radio-chemotherapy. GBM stem cells with this SNP showed lower levels of SEL1L expression and enhanced sensitivity to VPA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{camnasio_first_2012,

title = {The first reported generation of several induced pluripotent stem cell lines from homozygous and heterozygous Huntington's disease patients demonstrates mutation related enhanced lysosomal activity},

author = {Stefano Camnasio and Alessia {Delli Carri} and Angelo Lombardo and Iwona Grad and Caterina Mariotti and Alessia Castucci and Bj{ö}rn Rozell and Pietro {Lo Riso} and Valentina Castiglioni and Chiara Zuccato and Christelle Rochon and Yasuhiro Takashima and Giuseppe Diaferia and Ida Biunno and Cinzia Gellera and Marisa Jaconi and Austin Smith and Outi Hovatta and Luigi Naldini and Stefano {Di Donato} and Anis Feki and Elena Cattaneo},

doi = {10.1016/j.nbd.2011.12.042},

issn = {1095-953X},

year  = {2012},

date = {2012-04-01},

journal = {Neurobiology of Disease},

volume = {46},

number = {1},

pages = {41--51},

abstract = {Neuronal disorders, like Huntington's disease (HD), are difficult to study, due to limited cell accessibility, late onset manifestations, and low availability of material. The establishment of an in vitro model that recapitulates features of the disease may help understanding the cellular and molecular events that trigger disease manifestations. Here, we describe the generation and characterization of a series of induced pluripotent stem (iPS) cells derived from patients with HD, including two rare homozygous genotypes and one heterozygous genotype. We used lentiviral technology to transfer key genes for inducing reprogramming. To confirm pluripotency and differentiation of iPS cells, we used PCR amplification and immunocytochemistry to measure the expression of marker genes in embryoid bodies and neurons. We also analyzed teratomas that formed in iPS cell-injected mice. We found that the length of the pathological CAG repeat did not increase during reprogramming, after long term growth in vitro, and after differentiation into neurons. In addition, we observed no differences between normal and mutant genotypes in reprogramming, growth rate, caspase activation or neuronal differentiation. However, we observed a significant increase in lysosomal activity in HD-iPS cells compared to control iPS cells, both during self-renewal and in iPS-derived neurons. In conclusion, we have established stable HD-iPS cell lines that can be used for investigating disease mechanisms that underlie HD. The CAG stability and lysosomal activity represent novel observations in HD-iPS cells. In the future, these cells may provide the basis for a powerful platform for drug screening and target identification in HD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}